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1
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Ashfaq R, Kovács A, Berkó S, Budai-Szűcs M. Smart biomaterial gels for periodontal therapy: A novel approach. Biomed Pharmacother 2025; 183:117836. [PMID: 39832427 DOI: 10.1016/j.biopha.2025.117836] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2024] [Revised: 01/02/2025] [Accepted: 01/09/2025] [Indexed: 01/22/2025] Open
Abstract
Periodontitis, a chronic inflammatory condition of the oral cavity, is characterized by the progressive destruction of the supporting structures of the teeth. The pathogenic effects of periodontopathogens extend beyond the local periodontal environment, contributing to systemic health complications, thereby underscoring the need for effective therapeutic strategies. Current standard treatments, which involve mechanical debridement coupled with systemic anti-inflammatory and antibiotic therapies, are often associated with limited efficacy, adverse effects, and the emergence of antibiotic resistance. Recent advancements in localized drug delivery systems present an innovative alternative, offering site-specific targeting with sustained therapeutic action. Smart drug delivery platforms, designed to respond to the unique microenvironment of periodontal pockets, undergo physicochemical transformations such as gelation or controlled drug release, enhancing treatment efficacy. This review comprehensively explores the etiological and prognostic factors of periodontitis, critical diagnostic biomarkers, and an in-depth analysis of stimuli-responsive biomacromolecule-based gels. These systems are evaluated for their structural properties, biological compatibility, and therapeutic potential while addressing their limitations and barriers to clinical translation. By integrating insights into the interplay between material properties and biological performance, this review highlights the future role of these advanced delivery systems in overcoming challenges in periodontal healthcare. Such approaches aim to bridge the gap between bench-side innovation and bedside application, offering the transformative potential to enhance therapeutic outcomes and improve patient quality of life in managing periodontal diseases.
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Affiliation(s)
- Rabia Ashfaq
- Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, 6 Eötvös u., Szeged H-6720, Hungary
| | - Anita Kovács
- Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, 6 Eötvös u., Szeged H-6720, Hungary
| | - Szilvia Berkó
- Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, 6 Eötvös u., Szeged H-6720, Hungary
| | - Mária Budai-Szűcs
- Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, 6 Eötvös u., Szeged H-6720, Hungary.
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2
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Thakkar D, Sehgal R, Narula AK, Deswal D. Smart polymers: key to targeted therapeutic interventions. Chem Commun (Camb) 2024; 61:192-206. [PMID: 39611954 DOI: 10.1039/d4cc05098c] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2024]
Abstract
Smart polymers represent a class of advanced materials that undergo reversible changes in their physical or chemical form and are known as responsive polymers. These polymers show transitions when external stimuli, such as temperature and pH, come into play. Smart polymers are being increasingly applied in various fields, such as drug delivery to a targeted site and gene therapy. They also play a pivotal role in tissue engineering, environmental sensors, and the development of shape memory polymers. Despite their major challenges, they remain effective in overcoming significant barriers. It can be said that these polymers have the potential to revolutionize various fields. This review highlights the underlying types and applications of smart polymers, emphasizing their roles in the future.
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Affiliation(s)
- Divyanshi Thakkar
- Centre of Excellence in Pharmaceutical Sciences (CEPS), Guru Gobind Singh Indraprastha University (GGSIPU), New Delhi, India.
| | - Rhythm Sehgal
- Centre of Excellence in Pharmaceutical Sciences (CEPS), Guru Gobind Singh Indraprastha University (GGSIPU), New Delhi, India.
| | - A K Narula
- Centre of Excellence in Pharmaceutical Sciences (CEPS), Guru Gobind Singh Indraprastha University (GGSIPU), New Delhi, India.
| | - Deepa Deswal
- Centre of Excellence in Pharmaceutical Sciences (CEPS), Guru Gobind Singh Indraprastha University (GGSIPU), New Delhi, India.
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3
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Kim HJ, Jang J, Lee J, Han CH, Kim JW, Park BJ. Fabrication of Engineered Drug-Polymer Composite Particles via Piezoelectric Inkjet Technique for Floating Drug Delivery Systems. LANGMUIR : THE ACS JOURNAL OF SURFACES AND COLLOIDS 2024. [PMID: 39556093 DOI: 10.1021/acs.langmuir.4c03556] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2024]
Abstract
This study presents a simple approach for fabricating low-density drug-polymer amorphous solid dispersions (ASDs) using a piezoelectric inkjet method, demonstrating potential applications for floating drug delivery systems (FDDS). By adjusting the ratio of two polymers, polylactic acid, and Eudragit RLPO, the floatability and drug release rate of the drug-polymer ASD particles can be easily manipulated. Kinetic model analyses have been conducted to interpret the drug release mechanism. This work offers a robust platform for exploring diverse polymer-drug combinations that are applicable to FDDS.
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Affiliation(s)
- Hee Jin Kim
- Department of Chemical Engineering (BK21 FOUR Integrated Engineering Program), Kyung Hee University, Yongin 17104, South Korea
| | - Jiye Jang
- Department of Chemical Engineering (BK21 FOUR Integrated Engineering Program), Kyung Hee University, Yongin 17104, South Korea
| | - Jieun Lee
- Department of Chemical Engineering (BK21 FOUR Integrated Engineering Program), Kyung Hee University, Yongin 17104, South Korea
| | - Chang Hun Han
- Department of Chemical Engineering (BK21 FOUR Integrated Engineering Program), Kyung Hee University, Yongin 17104, South Korea
| | - Jin Woong Kim
- School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Bum Jun Park
- Department of Chemical Engineering (BK21 FOUR Integrated Engineering Program), Kyung Hee University, Yongin 17104, South Korea
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4
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Parashar AK, Saraogi GK, Jain PK, Kurmi B, Shrivastava V, Arora V. Polymer-drug conjugates: revolutionizing nanotheranostic agents for diagnosis and therapy. Discov Oncol 2024; 15:641. [PMID: 39527173 PMCID: PMC11554983 DOI: 10.1007/s12672-024-01509-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Accepted: 11/01/2024] [Indexed: 11/16/2024] Open
Abstract
Nanotheranostics, an amalgamation of therapeutic and diagnostic capabilities at the nanoscale, is revolutionizing personalized medicine. Polymer-drug conjugates (PDCs) stand at the forefront of this arena, offering a multifaceted approach to treat complex diseases such as cancer. This review explores the recent advancements in PDCs, highlighting their design principles, working mechanisms, and the therapeutic applications. We discuss the incorporation of imaging agents into PDCs that allow for real-time monitoring of drug delivery and treatment efficacy. With the aim of improving patient care, the review examines how PDCs enable targeted drug delivery, minimize side effects, and provide valuable diagnostic data, hence enhancing the precision of medical interventions. We also address the challenges facing the clinical translation of PDCs, such as scalability, regulatory hurdles, and cost-effectiveness, providing a comprehensive outlook on the future of nanotheranostics in patient management.
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Affiliation(s)
- Ashish Kumar Parashar
- Lloyd Institute of Management and Technology, Plot No.-11, Knowledge Park-II, Greater Noida, Uttar Pradesh, India, 201306.
| | | | | | - Balakdas Kurmi
- Department of Pharmaceutics, ISF College Pharmacy, GT Road, Moga, 142001, Punjab, India
| | | | - Vandana Arora
- Lloyd Institute of Management and Technology, Plot No.-11, Knowledge Park-II, Greater Noida, Uttar Pradesh, India, 201306
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5
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Cheng Y, Zhu M, Chi M, Lai Y, Li B, Qian R, Chen Z, Zhao G. MXene/TPU Hybrid Fabrics Enable Smart Wound Management and Thermoresponsive Drug Delivery. ACS APPLIED MATERIALS & INTERFACES 2024. [PMID: 38597358 DOI: 10.1021/acsami.3c19604] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/11/2024]
Abstract
Thermoresponsive wound dressings with real-time monitoring and on-demand drug delivery have gained significant attention recently. However, such smart systems with stable temperature adjustment and drug release control are still lacking. Here, a novel smart fabric is designed for wound management with thermoresponsive drug delivery and simultaneously temperature monitoring. The triple layers of the fabrics are composed of the drug-loaded thermoresponsive nanofiber film, the MXene-optimized joule heating film, and the FPCB control chip. The precise and stable temperature stimulation can be easily achieved by applying a low voltage (0-4 V) to the heating film, achieving the temperature control ranging from 25 to 130 °C. And the temperature of the wound region can be monitored and adjusted in real time, demonstrating an accurate and low-voltage joule heating capability. Based on that, the drug-loaded film achieved precise thermoresponsive drug release and obtained significant antibacterial effects in vitro. The in vivo experiments also proved the hybrid fabric system with a notable antibacterial effect and accelerated wound healing process (about 30% faster than the conventional gauze group).
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Affiliation(s)
- Yue Cheng
- School of Biomedical Engineering, Anhui Medical University, Hefei 230032, China
| | - Mengfei Zhu
- School of Biomedical Engineering, Anhui Medical University, Hefei 230032, China
| | - Mengqiao Chi
- School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China
| | - Yulin Lai
- School of Biomedical Engineering, Anhui Medical University, Hefei 230032, China
| | - Bing Li
- School of Biomedical Engineering, Anhui Medical University, Hefei 230032, China
| | - Rui Qian
- School of Biomedical Engineering, Anhui Medical University, Hefei 230032, China
| | - Zhongrong Chen
- School of Biomedical Engineering, Anhui Medical University, Hefei 230032, China
| | - Gang Zhao
- School of Biomedical Engineering, Anhui Medical University, Hefei 230032, China
- Department of Electronic Engineering and Information Science, University of Science and Technology of China, Hefei 230026, China
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6
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Hassani F, Heydarinasab A, Ahmad Panahi H, Moniri E. Surface modification of tungsten disulfide nanosheets with pH/Thermosensitive polymer and polyethylenimine dendrimer for near-infrared triggered drug delivery of letrozole. J Mol Liq 2023. [DOI: 10.1016/j.molliq.2022.121058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
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7
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Nazli A, He DL, Liao D, Khan MZI, Huang C, He Y. Strategies and progresses for enhancing targeted antibiotic delivery. Adv Drug Deliv Rev 2022; 189:114502. [PMID: 35998828 DOI: 10.1016/j.addr.2022.114502] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Revised: 08/10/2022] [Accepted: 08/16/2022] [Indexed: 01/24/2023]
Abstract
Antibiotic resistance is a global health issue and a potential risk for society. Antibiotics administered through conventional formulations are devoid of targeting effect and often spread to various undesired body sites, leading to sub-lethal concentrations at the site of action and thus resulting in emergence of resistance, as well as side effects. Moreover, we have a very slim antibiotic pipeline. Drug-delivery systems have been designed to control the rate, time, and site of drug release, and innovative approaches for antibiotic delivery provide a glint of hope for addressing these issues. This review elaborates different delivery strategies and approaches employed to overcome the limitations of conventional antibiotic therapy. These include antibiotic conjugates, prodrugs, and nanocarriers for local and targeted antibiotic release. In addition, a wide range of stimuli-responsive nanocarriers and biological carriers for targeted antibiotic delivery are discussed. The potential advantages and limitations of targeted antibiotic delivery strategies are described along with possible solutions to avoid these limitations. A number of antibiotics successfully delivered through these approaches with attained outcomes and potentials are reviewed.
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Affiliation(s)
- Adila Nazli
- Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, PR China
| | - David L He
- College of Chemistry, University of California, Berkeley, CA 94720, United States
| | - Dandan Liao
- Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, PR China
| | | | - Chao Huang
- Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, PR China.
| | - Yun He
- Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, PR China.
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8
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Farjadian F, Ghasemi S, Akbarian M, Hoseini-Ghahfarokhi M, Moghoofei M, Doroudian M. Physically stimulus-responsive nanoparticles for therapy and diagnosis. Front Chem 2022; 10:952675. [PMID: 36186605 PMCID: PMC9515617 DOI: 10.3389/fchem.2022.952675] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Accepted: 08/02/2022] [Indexed: 11/13/2022] Open
Abstract
Nanoparticles offer numerous advantages in various fields of science, particularly in medicine. Over recent years, the use of nanoparticles in disease diagnosis and treatments has increased dramatically by the development of stimuli-responsive nano-systems, which can respond to internal or external stimuli. In the last 10 years, many preclinical studies were performed on physically triggered nano-systems to develop and optimize stable, precise, and selective therapeutic or diagnostic agents. In this regard, the systems must meet the requirements of efficacy, toxicity, pharmacokinetics, and safety before clinical investigation. Several undesired aspects need to be addressed to successfully translate these physical stimuli-responsive nano-systems, as biomaterials, into clinical practice. These have to be commonly taken into account when developing physically triggered systems; thus, also applicable for nano-systems based on nanomaterials. This review focuses on physically triggered nano-systems (PTNSs), with diagnostic or therapeutic and theranostic applications. Several types of physically triggered nano-systems based on polymeric micelles and hydrogels, mesoporous silica, and magnets are reviewed and discussed in various aspects.
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Affiliation(s)
- Fatemeh Farjadian
- Pharmaceutical Sciences Research Center, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
- *Correspondence: Fatemeh Farjadian, , Soheila Ghasemi, , Mohammad Doroudian,
| | - Soheila Ghasemi
- Department of Chemistry, College of Sciences, Shiraz University, Shiraz, Iran
- *Correspondence: Fatemeh Farjadian, , Soheila Ghasemi, , Mohammad Doroudian,
| | - Mohsen Akbarian
- Department of Chemistry, National Cheng Kung University, Tainan, Taiwan
| | | | - Mohsen Moghoofei
- Department of Microbiology, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mohammad Doroudian
- Department of Cell and Molecular Sciences, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran
- *Correspondence: Fatemeh Farjadian, , Soheila Ghasemi, , Mohammad Doroudian,
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9
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Ye S, Wei B, Zeng L. Advances on Hydrogels for Oral Science Research. Gels 2022; 8:gels8050302. [PMID: 35621600 PMCID: PMC9140480 DOI: 10.3390/gels8050302] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 04/22/2022] [Accepted: 04/25/2022] [Indexed: 11/16/2022] Open
Abstract
Hydrogels are biocompatible polymer systems, which have become a hotspot in biomedical research. As hydrogels mimic the structure of natural extracellular matrices, they are considered as good scaffold materials in the tissue engineering area for repairing dental pulp and periodontal damages. Combined with different kinds of stem cells and growth factors, various hydrogel complexes have played an optimistic role in endodontic and periodontal tissue engineering studies. Further, hydrogels exhibit biological effects in response to external stimuli, which results in hydrogels having a promising application in local drug delivery. This review summarized the advances of hydrogels in oral science research, in the hopes of providing a reference for future applications.
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Affiliation(s)
- Shengjia Ye
- Department of Prosthodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China;
- College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Engineering Research Center of Advanced Dental Technology and Materials, Shanghai 200011, China
| | - Bin Wei
- College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Engineering Research Center of Advanced Dental Technology and Materials, Shanghai 200011, China
- Department of Stomatology Special Consultation Clinic, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
- Correspondence: (B.W.); (L.Z.)
| | - Li Zeng
- Department of Prosthodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China;
- College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Engineering Research Center of Advanced Dental Technology and Materials, Shanghai 200011, China
- Correspondence: (B.W.); (L.Z.)
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10
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A Novel Strategy for Poly(β-alanine-b-lactone)s: Sequentially HTP and AROP. Macromol Res 2022. [DOI: 10.1007/s13233-022-0034-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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11
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Kudryavtseva V, Bukatin A, Vyacheslavova E, Gould D, Sukhorukov GB. Printed asymmetric microcapsules: Facile loading and multiple stimuli-responsiveness. BIOMATERIALS ADVANCES 2022; 136:212762. [PMID: 35929328 DOI: 10.1016/j.bioadv.2022.212762] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 03/08/2022] [Accepted: 03/12/2022] [Indexed: 06/15/2023]
Abstract
Engineering of colloidal particles and capsules despite substantial progress is still facing a number of unsolved issues including low loading capacity, non-uniform size and shape of carriers, tailoring different functionalities and versatility to encapsulated cargo. In this work, we propose a method for defined-shaped functionally asymmetric polymer capsule fabrication based on a soft lithography approach. The developed capsules consist of two classes of polymers - the main part "cup" is made out of polyelectrolyte multilayers (PAH-PSS) and "lid" is made of biodegradable polyether (PLGA). Asymmetric capsules combine advantages from both traditional layer-by-layer capsules and recently developed printed "pelmeni" capsules. This combination provides stimuli-responsiveness due to polyelectrolyte multilayer properties differing from PLGA. The inner volume of capsules can be loaded with a variety of active compounds and the capsule's geometry is defined due to the soft-lithography method. Capsules have a core-shell structure and monodisperse size distribution. Three methods to trigger cargo release have been demonstrated, namely temperature treatment, ultrasonication and pH shift. Steroidal drug dexamethasone was used to illustrate the applicability of the systems for triggered drug release. The application of proposed asymmetric capsules includes but is not limited to pharmacology, diagnostics, sensors, micro- and nanoreactors and chemical actuators.
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Affiliation(s)
- Valeriya Kudryavtseva
- Nanoforce Technology Ltd, School of Engineering and Materials Science, Queen Mary University of London, London, E1 4NS, United Kingdom; National Research Tomsk Polytechnic University, 30 Lenin Avenue, Tomsk 634050, Russian Federation
| | - Anton Bukatin
- Alferov Saint Petersburg National Research Academic University of the Russian Academy of Sciences, 8/3A Khlopina str, Saint Petersburg 194021, Russia; Institute for Analytical Instrumentation of the Russian Academy of Sciences, 31-33 A, Ivana Chernykh str., Saint Petersburg 198095, Russia
| | - Ekaterina Vyacheslavova
- Alferov Saint Petersburg National Research Academic University of the Russian Academy of Sciences, 8/3A Khlopina str, Saint Petersburg 194021, Russia
| | - David Gould
- Biochemical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London EC1M 6BQ, United Kingdom
| | - Gleb B Sukhorukov
- Nanoforce Technology Ltd, School of Engineering and Materials Science, Queen Mary University of London, London, E1 4NS, United Kingdom; Skolkovo Institute of Science and Technology, Bolshoy Boulevard 30, bld. 1, Moscow 121205, Russian Federation; Siberian State Medical University, Moskovskiy Trakt, 2, Tomsk 634050, Russia.
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12
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NVCL-Based Hydrogels and Composites for Biomedical Applications: Progress in the Last Ten Years. Int J Mol Sci 2022; 23:ijms23094722. [PMID: 35563114 PMCID: PMC9103572 DOI: 10.3390/ijms23094722] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2022] [Revised: 04/22/2022] [Accepted: 04/22/2022] [Indexed: 12/20/2022] Open
Abstract
Hydrogels consist of three-dimensionally crosslinked polymeric chains, are hydrophilic, have the ability to absorb other molecules in their structure and are relatively easy to obtain. However, in order to improve some of their properties, usually mechanical, or to provide them with some physical, chemical or biological characteristics, hydrogels have been synthesized combined with other synthetic or natural polymers, filled with inorganic nanoparticles, metals, and even polymeric nanoparticles, giving rise to composite hydrogels. In general, different types of hydrogels have been synthesized; however, in this review, we refer to those obtained from the thermosensitive polymer poly(N-vinylcaprolactam) (PNVCL) and we focus on the definition, properties, synthesis techniques, nanomaterials used as fillers in composites and mainly applications of PNVCL-based hydrogels in the biomedical area. This type of material has great potential in biomedical applications such as drug delivery systems, tissue engineering, as antimicrobials and in diagnostic and bioimaging.
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13
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Smart gating porous particles as new carriers for drug delivery. Adv Drug Deliv Rev 2021; 174:425-446. [PMID: 33930490 DOI: 10.1016/j.addr.2021.04.023] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Revised: 04/12/2021] [Accepted: 04/23/2021] [Indexed: 12/13/2022]
Abstract
The design of smart drug delivery carriers has recently attracted great attention in the biomedical field. Smart carriers can specifically respond to physical and chemical changes in their environment, such as temperature, photoirradiation, ultrasound, magnetic field, pH, redox species, and biomolecules. This review summarizes recent advances in the integration of porous particles and stimuli-responsive gatekeepers for effective drug delivery. Their unique structural properties play an important role in facilitating the diffusion of drug molecules and cell attachment. Various techniques for fabricating porous materials, with their major advantages and limitations, are summarized. Smart gatekeepers provide advanced functions such as "open-close" switching by functionalized stimuli-responsive polymers on a particle's pores. These controlled delivery systems enable drugs to be targeted at specific rates, time programs, and sites of the human body. The gate structures, gating mechanisms, and controlled release mechanisms of each trigger are detailed. Current ongoing research and future trends in targeted drug delivery, tissue engineering, and regenerative medicine applications are highlighted.
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14
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Castillo-Henríquez L, Castro-Alpízar J, Lopretti-Correa M, Vega-Baudrit J. Exploration of Bioengineered Scaffolds Composed of Thermo-Responsive Polymers for Drug Delivery in Wound Healing. Int J Mol Sci 2021; 22:1408. [PMID: 33573351 PMCID: PMC7866792 DOI: 10.3390/ijms22031408] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Revised: 01/13/2021] [Accepted: 01/27/2021] [Indexed: 02/06/2023] Open
Abstract
Innate and adaptive immune responses lead to wound healing by regulating a complex series of events promoting cellular cross-talk. An inflammatory response is presented with its characteristic clinical symptoms: heat, pain, redness, and swelling. Some smart thermo-responsive polymers like chitosan, polyvinylpyrrolidone, alginate, and poly(ε-caprolactone) can be used to create biocompatible and biodegradable scaffolds. These processed thermo-responsive biomaterials possess 3D architectures similar to human structures, providing physical support for cell growth and tissue regeneration. Furthermore, these structures are used as novel drug delivery systems. Locally heated tumors above the polymer lower the critical solution temperature and can induce its conversion into a hydrophobic form by an entropy-driven process, enhancing drug release. When the thermal stimulus is gone, drug release is reduced due to the swelling of the material. As a result, these systems can contribute to the wound healing process in accelerating tissue healing, avoiding large scar tissue, regulating the inflammatory response, and protecting from bacterial infections. This paper integrates the relevant reported contributions of bioengineered scaffolds composed of smart thermo-responsive polymers for drug delivery applications in wound healing. Therefore, we present a comprehensive review that aims to demonstrate these systems' capacity to provide spatially and temporally controlled release strategies for one or more drugs used in wound healing. In this sense, the novel manufacturing techniques of 3D printing and electrospinning are explored for the tuning of their physicochemical properties to adjust therapies according to patient convenience and reduce drug toxicity and side effects.
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Affiliation(s)
- Luis Castillo-Henríquez
- National Laboratory of Nanotechnology (LANOTEC), National Center for High Technology (CeNAT), 1174-1200 San José, Costa Rica;
- Physical Chemistry Laboratory, Faculty of Pharmacy, University of Costa Rica, 11501-2060 San José, Costa Rica
| | - Jose Castro-Alpízar
- Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Costa Rica, 11501-2060 San José, Costa Rica;
| | - Mary Lopretti-Correa
- Nuclear Research Center, Faculty of Science, Universidad de la República (UdelaR), 11300 Montevideo, Uruguay;
| | - José Vega-Baudrit
- National Laboratory of Nanotechnology (LANOTEC), National Center for High Technology (CeNAT), 1174-1200 San José, Costa Rica;
- Laboratory of Polymers (POLIUNA), Chemistry School, National University of Costa Rica, 86-3000 Heredia, Costa Rica
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15
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Hogan KJ, Mikos AG. Biodegradable thermoresponsive polymers: Applications in drug delivery and tissue engineering. POLYMER 2020. [DOI: 10.1016/j.polymer.2020.123063] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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16
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Moradi Kashkooli F, Soltani M, Souri M. Controlled anti-cancer drug release through advanced nano-drug delivery systems: Static and dynamic targeting strategies. J Control Release 2020; 327:316-349. [PMID: 32800878 DOI: 10.1016/j.jconrel.2020.08.012] [Citation(s) in RCA: 252] [Impact Index Per Article: 50.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 08/07/2020] [Accepted: 08/08/2020] [Indexed: 12/14/2022]
Abstract
Advances in nanomedicine, including early cancer detection, targeted drug delivery, and personalized approaches to cancer treatment are on the rise. For example, targeted drug delivery systems can improve intracellular delivery because of their multifunctionality. Novel endogenous-based and exogenous-based stimulus-responsive drug delivery systems have been proposed to prevent the cancer progression with proper drug delivery. To control effective dose loading and sustained release, targeted permeability and individual variability can now be described in more-complex ways, such as by combining internal and external stimuli. Despite these advances in release control, certain challenges remain and are identified in this research, which emphasizes the control of drug release and applications of nanoparticle-based drug delivery systems. Using a multiscale and multidisciplinary approach, this study investigates and analyzes drug delivery and release strategies in the nanoparticle-based treatment of cancer, both mathematically and clinically.
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Affiliation(s)
- Farshad Moradi Kashkooli
- Department of Mechanical Engineering, K. N. Toosi University of Technology, Tehran, Iran; Department of Applied Mathematics, University of Waterloo, Waterloo, ON, Canada..
| | - M Soltani
- Department of Mechanical Engineering, K. N. Toosi University of Technology, Tehran, Iran; Advanced Bioengineering Initiative Center, Computational Medicine Center, K. N. Toosi University of Technology, Tehran, Iran; Department of Electrical and Computer Engineering, University of Waterloo, Waterloo, ON, Canada; Centre for Biotechnology and Bioengineering (CBB), University of Waterloo, Waterloo, ON, Canada; Cancer Biology Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran.
| | - Mohammad Souri
- Department of Mechanical Engineering, K. N. Toosi University of Technology, Tehran, Iran.
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Park JR, Sarwat M, Bolle ECL, de Laat MA, Van Guyse JFR, Podevyn A, Hoogenboom R, Dargaville TR. Drug–polymer conjugates with dynamic cloud point temperatures based on poly(2-oxazoline) copolymers. Polym Chem 2020. [DOI: 10.1039/d0py00602e] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
A shift in cloud point temperatures of poly(2-oxazoline)/ACE inhibitor polymer drug conjugates occurs on release of the drug.
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Affiliation(s)
- Jong-Ryul Park
- Institute of Health and Biomedical Innovation
- Science and Engineering Faculty
- Queensland University of Technology
- Australia
| | - Mariah Sarwat
- Institute of Health and Biomedical Innovation
- Science and Engineering Faculty
- Queensland University of Technology
- Australia
| | - Eleonore C. L. Bolle
- Institute of Health and Biomedical Innovation
- Science and Engineering Faculty
- Queensland University of Technology
- Australia
| | - Melody A. de Laat
- Institute of Health and Biomedical Innovation
- Science and Engineering Faculty
- Queensland University of Technology
- Australia
| | - Joachim F. R. Van Guyse
- Supramolecular Chemistry Group
- Centre of Macromolecular Chemistry (CMaC)
- Department of Organic and Macromolecular Chemistry
- Ghent University
- B-9000 Ghent
| | - Annelore Podevyn
- Supramolecular Chemistry Group
- Centre of Macromolecular Chemistry (CMaC)
- Department of Organic and Macromolecular Chemistry
- Ghent University
- B-9000 Ghent
| | - Richard Hoogenboom
- Supramolecular Chemistry Group
- Centre of Macromolecular Chemistry (CMaC)
- Department of Organic and Macromolecular Chemistry
- Ghent University
- B-9000 Ghent
| | - Tim R. Dargaville
- Institute of Health and Biomedical Innovation
- Science and Engineering Faculty
- Queensland University of Technology
- Australia
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18
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Abri Aghdam M, Bagheri R, Mosafer J, Baradaran B, Hashemzaei M, Baghbanzadeh A, de la Guardia M, Mokhtarzadeh A. Recent advances on thermosensitive and pH-sensitive liposomes employed in controlled release. J Control Release 2019; 315:1-22. [DOI: 10.1016/j.jconrel.2019.09.018] [Citation(s) in RCA: 141] [Impact Index Per Article: 23.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Revised: 09/26/2019] [Accepted: 09/27/2019] [Indexed: 12/12/2022]
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19
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Khurana B, Gierlich P, Meindl A, Gomes-da-Silva LC, Senge MO. Hydrogels: soft matters in photomedicine. Photochem Photobiol Sci 2019; 18:2613-2656. [PMID: 31460568 DOI: 10.1039/c9pp00221a] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Photodynamic therapy (PDT), a shining beacon in the realm of photomedicine, is a non-invasive technique that utilizes dye-based photosensitizers (PSs) in conjunction with light and oxygen to produce reactive oxygen species to combat malignant tissues and infectious microorganisms. Yet, for PDT to become a common, routine therapy, it is still necessary to overcome limitations such as photosensitizer solubility, long-term side effects (e.g., photosensitivity) and to develop safe, biocompatible and target-specific formulations. Polymer based drug delivery platforms are an effective strategy for the delivery of PSs for PDT applications. Among them, hydrogels and 3D polymer scaffolds with the ability to swell in aqueous media have been deeply investigated. Particularly, hydrogel-based formulations present real potential to fulfill all requirements of an ideal PDT platform by overcoming the solubility issues, while improving the selectivity and targeting drawbacks of the PSs alone. In this perspective, we summarize the use of hydrogels as carrier systems of PSs to enhance the effectiveness of PDT against infections and cancer. Their potential in environmental and biomedical applications, such as tissue engineering photoremediation and photochemistry, is also discussed.
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Affiliation(s)
- Bhavya Khurana
- Medicinal Chemistry, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, Trinity College Dublin, The University of Dublin, St James's Hospital, Dublin 8, Ireland.
| | - Piotr Gierlich
- Medicinal Chemistry, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, Trinity College Dublin, The University of Dublin, St James's Hospital, Dublin 8, Ireland. and CQC, Coimbra Chemistry Department, University of Coimbra, Coimbra, Portugal
| | - Alina Meindl
- Physik Department E20, Technische Universität München, James-Franck-Str. 1, 85748 Garching, Germany
| | | | - Mathias O Senge
- Medicinal Chemistry, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, Trinity College Dublin, The University of Dublin, St James's Hospital, Dublin 8, Ireland. and Physik Department E20, Technische Universität München, James-Franck-Str. 1, 85748 Garching, Germany and Institute for Advanced Study (TUM-IAS), Technische Universität München, Lichtenberg-Str. 2a, 85748 Garching, Germany
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20
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Budkov YA, Kolesnikov AL. Models of the Conformational Behavior of Polymers in Mixed Solvents. POLYMER SCIENCE SERIES C 2018. [DOI: 10.1134/s1811238218020030] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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21
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Altomare L, Bonetti L, Campiglio CE, De Nardo L, Draghi L, Tana F, Farè S. Biopolymer-based strategies in the design of smart medical devices and artificial organs. Int J Artif Organs 2018; 41:337-359. [PMID: 29614899 PMCID: PMC6159845 DOI: 10.1177/0391398818765323] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2017] [Accepted: 02/26/2018] [Indexed: 12/31/2022]
Abstract
Advances in regenerative medicine and in modern biomedical therapies are fast evolving and set goals causing an upheaval in the field of materials science. This review discusses recent developments involving the use of biopolymers as smart materials, in terms of material properties and stimulus-responsive behavior, in the presence of environmental physico-chemical changes. An overview on the transformations that can be triggered in natural-based polymeric systems (sol-gel transition, polymer relaxation, cross-linking, and swelling) is presented, with specific focus on the benefits these materials can provide in biomedical applications.
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Affiliation(s)
- Lina Altomare
- Department of Chemistry, Materials and Chemical Engineering “Giulio Natta,” Politecnico di Milano, Milano, Italy
- National Interuniversity Consortium of Materials Science and Technology (INSTM), Firenze, Italy
| | - Lorenzo Bonetti
- Department of Chemistry, Materials and Chemical Engineering “Giulio Natta,” Politecnico di Milano, Milano, Italy
- National Interuniversity Consortium of Materials Science and Technology (INSTM), Firenze, Italy
| | - Chiara E Campiglio
- Department of Chemistry, Materials and Chemical Engineering “Giulio Natta,” Politecnico di Milano, Milano, Italy
- National Interuniversity Consortium of Materials Science and Technology (INSTM), Firenze, Italy
| | - Luigi De Nardo
- Department of Chemistry, Materials and Chemical Engineering “Giulio Natta,” Politecnico di Milano, Milano, Italy
- National Interuniversity Consortium of Materials Science and Technology (INSTM), Firenze, Italy
| | - Lorenza Draghi
- Department of Chemistry, Materials and Chemical Engineering “Giulio Natta,” Politecnico di Milano, Milano, Italy
- National Interuniversity Consortium of Materials Science and Technology (INSTM), Firenze, Italy
| | - Francesca Tana
- Department of Chemistry, Materials and Chemical Engineering “Giulio Natta,” Politecnico di Milano, Milano, Italy
- National Interuniversity Consortium of Materials Science and Technology (INSTM), Firenze, Italy
| | - Silvia Farè
- Department of Chemistry, Materials and Chemical Engineering “Giulio Natta,” Politecnico di Milano, Milano, Italy
- National Interuniversity Consortium of Materials Science and Technology (INSTM), Firenze, Italy
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22
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Budkov YA, Kiselev MG. Flory-type theories of polymer chains under different external stimuli. JOURNAL OF PHYSICS. CONDENSED MATTER : AN INSTITUTE OF PHYSICS JOURNAL 2018; 30:043001. [PMID: 29271365 DOI: 10.1088/1361-648x/aa9f56] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
In this Review, we present a critical analysis of various applications of the Flory-type theories to a theoretical description of the conformational behavior of single polymer chains in dilute polymer solutions under a few external stimuli. Different theoretical models of flexible polymer chains in the supercritical fluid are discussed and analysed. Different points of view on the conformational behavior of the polymer chain near the liquid-gas transition critical point of the solvent are presented. A theoretical description of the co-solvent-induced coil-globule transitions within the implicit-solvent-explicit-co-solvent models is discussed. Several explicit-solvent-explicit-co-solvent theoretical models of the coil-to-globule-to-coil transition of the polymer chain in a mixture of good solvents (co-nonsolvency) are analysed and compared with each other. Finally, a new theoretical model of the conformational behavior of the dielectric polymer chain under the external constant electric field in the dilute polymer solution with an explicit account for the many-body dipole correlations is discussed. The polymer chain collapse induced by many-body dipole correlations of monomers in the context of statistical thermodynamics of dielectric polymers is analysed.
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Affiliation(s)
- Yu A Budkov
- Tikhonov Moscow Institute of Electronics and Mathematics, School of Applied Mathematics, National Research University Higher School of Economics, Moscow, Russia. Laboratory of NMR Spectroscopy and Numerical Investigations of Liquids, G.A. Krestov Institute of Solution Chemistry of the Russian Academy of Sciences, Ivanovo, Russia
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23
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Tang X, Loc WS, Dong C, Matters GL, Butler PJ, Kester M, Meyers C, Jiang Y, Adair JH. The use of nanoparticulates to treat breast cancer. Nanomedicine (Lond) 2017; 12:2367-2388. [PMID: 28868970 DOI: 10.2217/nnm-2017-0202] [Citation(s) in RCA: 56] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Breast cancer is a major ongoing public health issue among women in both developing and developed countries. Significant progress has been made to improve the breast cancer treatment in the past decades. However, the current clinical approaches are invasive, of low specificity and can generate severe side effects. As a rapidly developing field, nanotechnology brings promising opportunities to human cancer diagnosis and treatment. The use of nanoparticulate-based platforms overcomes biological barriers and allows prolonged blood circulation time, simultaneous tumor targeting and enhanced accumulation of drugs in tumors. Currently available and clinically applicable innovative nanoparticulate-based systems for breast cancer nanotherapies are discussed in this review.
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Affiliation(s)
- Xiaomeng Tang
- Department of Chemistry, Pennsylvania State University, University Park, PA 16802, USA.,Department of Materials Science & Engineering, Pennsylvania State University, University Park, PA 16802, USA
| | - Welley S Loc
- Department of Chemistry, Pennsylvania State University, University Park, PA 16802, USA.,Department of Materials Science & Engineering, Pennsylvania State University, University Park, PA 16802, USA
| | - Cheng Dong
- Department of Bioengineering, Pennsylvania State University, University Park, PA 16802, USA
| | - Gail L Matters
- Department of Biochemistry & Molecular Biology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
| | - Peter J Butler
- Department of Bioengineering, Pennsylvania State University, University Park, PA 16802, USA
| | - Mark Kester
- Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
| | - Craig Meyers
- Department of Microbiology & Immunology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
| | - Yixing Jiang
- Marlene & Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA
| | - James H Adair
- Department of Materials Science & Engineering, Pennsylvania State University, University Park, PA 16802, USA
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24
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Spontaneously formed redox- and pH-sensitive polymersomes by mPEG based cytocompatible random copolymers. J Colloid Interface Sci 2017; 501:22-33. [DOI: 10.1016/j.jcis.2017.04.034] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2017] [Revised: 04/09/2017] [Accepted: 04/10/2017] [Indexed: 01/05/2023]
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25
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Budkov YA, Kalikin NN, Kolesnikov AL. Polymer chain collapse induced by many-body dipole correlations. THE EUROPEAN PHYSICAL JOURNAL. E, SOFT MATTER 2017; 40:47. [PMID: 28417323 DOI: 10.1140/epje/i2017-11533-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/06/2017] [Accepted: 03/17/2017] [Indexed: 06/07/2023]
Abstract
We present a simple analytical theory of a flexible polymer chain dissolved in a good solvent, carrying permanent freely oriented dipoles on the monomers. We take into account the dipole correlations within the random phase approximation (RPA), as well as a dielectric heterogeneity in the internal polymer volume relative to the bulk solution. We demonstrate that the dipole correlations of monomers can be taken into account as pairwise ones only when the polymer chain is in a coil conformation. In this case the dipole correlations manifest themselves through the Keesom interactions of the permanent dipoles. On the other hand, the dielectric heterogeneity effect (dielectric mismatch effect) leads to the effective interaction between the monomers of the polymeric coil. Both of these effects can be taken into account by renormalizing the second virial coefficient of the monomer-monomer volume interactions. We establish that in the case when the solvent dielectric permittivity exceeds the dielectric permittivity of the polymeric material, the dielectric mismatch effect competes with the dipole attractive interactions, leading to polymer coil expansion. In the opposite case, both the dielectric mismatch effect and the dipole attractive interaction lead to the polymer coil collapse. We analyse the coil-globule transition caused by the dipole correlations of monomers within the many-body theory. We demonstrate that accounting for the dipole correlations higher than the pairwise ones smooths this pure electrostatics driven coil-globule transition of the polymer chain.
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Affiliation(s)
- Yu A Budkov
- National Research University Higher School of Economics, Department of Applied Mathematics, Moscow, Russia.
| | - N N Kalikin
- Ivanovo State University, Department of Physics, Ivanovo, Russia
| | - A L Kolesnikov
- Institut für Nichtklassische Chemie e.V., Universität Leipzig, Leipzig, Germany
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26
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Dynamic, ultra-pH-sensitive graft copolymer micelles mediated rapid, complete destruction of 3-D tumor spheroids in vitro. POLYMER 2017. [DOI: 10.1016/j.polymer.2017.01.054] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
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27
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Kumar S, Rani R, Dilbaghi N, Tankeshwar K, Kim KH. Carbon nanotubes: a novel material for multifaceted applications in human healthcare. Chem Soc Rev 2017; 46:158-196. [DOI: 10.1039/c6cs00517a] [Citation(s) in RCA: 263] [Impact Index Per Article: 32.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Remarkable advances achieved in modern material technology, especially in device fabrication, have facilitated diverse materials to expand the list of their application fields.
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Affiliation(s)
- Sandeep Kumar
- Department of Bio and Nano Technology
- Guru Jambheshwar University of Science and Technology
- Hisar
- India
| | - Ruma Rani
- Department of Bio and Nano Technology
- Guru Jambheshwar University of Science and Technology
- Hisar
- India
| | - Neeraj Dilbaghi
- Department of Bio and Nano Technology
- Guru Jambheshwar University of Science and Technology
- Hisar
- India
| | - K. Tankeshwar
- Department of Bio and Nano Technology
- Guru Jambheshwar University of Science and Technology
- Hisar
- India
- Department of Physics
| | - Ki-Hyun Kim
- Department of Civil & Environmental Engineering
- Hanyang University
- Seoul 04763
- Republic of Korea
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28
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Wang J, Kaplan JA, Colson YL, Grinstaff MW. Mechanoresponsive materials for drug delivery: Harnessing forces for controlled release. Adv Drug Deliv Rev 2017; 108:68-82. [PMID: 27856307 PMCID: PMC5285479 DOI: 10.1016/j.addr.2016.11.001] [Citation(s) in RCA: 70] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2016] [Revised: 11/01/2016] [Accepted: 11/09/2016] [Indexed: 12/15/2022]
Abstract
Mechanically-activated delivery systems harness existing physiological and/or externally-applied forces to provide spatiotemporal control over the release of active agents. Current strategies to deliver therapeutic proteins and drugs use three types of mechanical stimuli: compression, tension, and shear. Based on the intended application, each stimulus requires specific material selection, in terms of substrate composition and size (e.g., macrostructured materials and nanomaterials), for optimal in vitro and in vivo performance. For example, compressive systems typically utilize hydrogels or elastomeric substrates that respond to and withstand cyclic compressive loading, whereas, tension-responsive systems use composites to compartmentalize payloads. Finally, shear-activated systems are based on nanoassemblies or microaggregates that respond to physiological or externally-applied shear stresses. In order to provide a comprehensive assessment of current research on mechanoresponsive drug delivery, the mechanical stimuli intrinsically present in the human body are first discussed, along with the mechanical forces typically applied during medical device interventions, followed by in-depth descriptions of compression, tension, and shear-mediated drug delivery devices. We conclude by summarizing the progress of current research aimed at integrating mechanoresponsive elements within these devices, identifying additional clinical opportunities for mechanically-activated systems, and discussing future prospects.
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Affiliation(s)
- Julia Wang
- Department of Biomedical Engineering, Boston University, 590 Commonwealth Avenue, Boston, MA 02215, United States
| | - Jonah A Kaplan
- Department of Biomedical Engineering, Boston University, 590 Commonwealth Avenue, Boston, MA 02215, United States
| | - Yolonda L Colson
- Division of Thoracic Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115, United States
| | - Mark W Grinstaff
- Department of Biomedical Engineering, Boston University, 590 Commonwealth Avenue, Boston, MA 02215, United States; Department of Chemistry, Boston University, 590 Commonwealth Avenue, Boston, MA 02215, United States; Department of Medicine, Boston University, 590 Commonwealth Avenue, Boston, MA 02215, United States.
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29
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Marquez DT, Scaiano JC. Visible and Near-Infrared Plasmon-Mediated Molecular Release from Cucurbit[6]uril Mesoporous Gated Systems. LANGMUIR : THE ACS JOURNAL OF SURFACES AND COLLOIDS 2016; 32:13764-13770. [PMID: 27936764 DOI: 10.1021/acs.langmuir.6b03679] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
Several hybrid mesoporous materials were synthesized in order to obtain a drug/cargo delivery system in which it is possible to control both the start and rate of the cargo release via surface plasmon (SPR) excitation. The successful incorporation of a thermoresponsive gate based on a cucurbit[6]uril-hexamethylene diamine (CB6-Hex) host-guest complex conferred the system with the desired "zero" premature release. This feature combined with the incorporation of gold nanorods (AuNR) and gold nanoparticles (AuNP) capable of acting as a heat source upon SPR excitation enabled a controlled cargo release system active to green and NIR irradiation. The results obtained prove that it is possible to disassemble the CB6-Hex gate complex in a few minutes using either green or NIR irradiation in order to activate the system and start the release process (that can take hours), as well as to further control the diffusion of Naproxen as a model drug.
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Affiliation(s)
- Daniela T Marquez
- Department of Chemistry and Biomolecular Sciences and Centre for Catalysis Research and Innovation, University of Ottawa , 10, Marie Curie, Ottawa, Ontario K1N6N5, Canada
| | - Juan C Scaiano
- Department of Chemistry and Biomolecular Sciences and Centre for Catalysis Research and Innovation, University of Ottawa , 10, Marie Curie, Ottawa, Ontario K1N6N5, Canada
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30
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Katz E. Modified Electrodes and Electrochemical Systems Switchable by Temperature Changes. ELECTROANAL 2016. [DOI: 10.1002/elan.201600235] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Affiliation(s)
- Evgeny Katz
- Department of Chemistry and Biomolecular Science; Clarkson University; Potsdam NY 13699-5810 USA
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31
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Karimi M, Ghasemi A, Sahandi Zangabad P, Rahighi R, Moosavi Basri SM, Mirshekari H, Amiri M, Shafaei Pishabad Z, Aslani A, Bozorgomid M, Ghosh D, Beyzavi A, Vaseghi A, Aref AR, Haghani L, Bahrami S, Hamblin MR. Smart micro/nanoparticles in stimulus-responsive drug/gene delivery systems. Chem Soc Rev 2016; 45:1457-501. [PMID: 26776487 PMCID: PMC4775468 DOI: 10.1039/c5cs00798d] [Citation(s) in RCA: 959] [Impact Index Per Article: 106.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
New achievements in the realm of nanoscience and innovative techniques of nanomedicine have moved micro/nanoparticles (MNPs) to the point of becoming actually useful for practical applications in the near future. Various differences between the extracellular and intracellular environments of cancerous and normal cells and the particular characteristics of tumors such as physicochemical properties, neovasculature, elasticity, surface electrical charge, and pH have motivated the design and fabrication of inventive "smart" MNPs for stimulus-responsive controlled drug release. These novel MNPs can be tailored to be responsive to pH variations, redox potential, enzymatic activation, thermal gradients, magnetic fields, light, and ultrasound (US), or can even be responsive to dual or multi-combinations of different stimuli. This unparalleled capability has increased their importance as site-specific controlled drug delivery systems (DDSs) and has encouraged their rapid development in recent years. An in-depth understanding of the underlying mechanisms of these DDS approaches is expected to further contribute to this groundbreaking field of nanomedicine. Smart nanocarriers in the form of MNPs that can be triggered by internal or external stimulus are summarized and discussed in the present review, including pH-sensitive peptides and polymers, redox-responsive micelles and nanogels, thermo- or magnetic-responsive nanoparticles (NPs), mechanical- or electrical-responsive MNPs, light or ultrasound-sensitive particles, and multi-responsive MNPs including dual stimuli-sensitive nanosheets of graphene. This review highlights the recent advances of smart MNPs categorized according to their activation stimulus (physical, chemical, or biological) and looks forward to future pharmaceutical applications.
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Affiliation(s)
- Mahdi Karimi
- Department of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Amir Ghasemi
- Department of Materials Science and Engineering, Sharif University of Technology, 11365-9466, Tehran, Iran
| | - Parham Sahandi Zangabad
- Department of Materials Science and Engineering, Sharif University of Technology, 11365-9466, Tehran, Iran
| | - Reza Rahighi
- Department of Research and Development, Sharif Ultrahigh Nanotechnologists (SUN) Company, P.O. Box: 13488-96394, Tehran, Iran and Nanotechnology Research Center, Research Institute of Petroleum Industry (RIPI), West Entrance Blvd., Olympic Village, P.O. Box: 14857-33111, Tehran, Iran
| | - S Masoud Moosavi Basri
- Bioenvironmental Research Center, Sharif University of Technology, Tehran, Iran and Civil & Environmental Engineering Department, Shahid Beheshti University, Tehran, Iran
| | - H Mirshekari
- Department of Biotechnology, University of Kerala, Trivandrum, India
| | - M Amiri
- Department of Materials Science and Engineering, Sharif University of Technology, 11365-9466, Tehran, Iran
| | - Z Shafaei Pishabad
- Department of Cell & Molecular Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran
| | - A Aslani
- Department of Materials Science and Engineering, Sharif University of Technology, 11365-9466, Tehran, Iran
| | - M Bozorgomid
- Department of Applied Chemistry, Central Branch of Islamic Azad University of Tehran, Tehran, Iran
| | - D Ghosh
- Department of Medical Nanotechnology, School of Advanced Technologies in Medicine (SATiM), Tehran University of Medical Sciences, Tehran, Iran
| | - A Beyzavi
- School of Mechanical Engineering, Boston University, Boston, MA, USA
| | - A Vaseghi
- Department of Biotechnology, Faculty of Advanced Science and Technologies of Isfahan, Isfahan, Iran
| | - A R Aref
- Department of Cancer Biology, Center for Cancer Systems Biology, Dana-Farber Cancer Institute, Department of Genetics, Harvard Medical School, Boston, MA 02215, USA
| | - L Haghani
- School of Medicine, International Campus of Tehran University of Medical Science, Tehran, Iran
| | - S Bahrami
- Department of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Michael R Hamblin
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA. and Department of Dermatology, Harvard Medical School, Boston, MA 02115, USA and Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139, USA
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32
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Kamps JAAM, Krenning G. Micromanaging cardiac regeneration: Targeted delivery of microRNAs for cardiac repair and regeneration. World J Cardiol 2016; 8:163-179. [PMID: 26981212 PMCID: PMC4766267 DOI: 10.4330/wjc.v8.i2.163] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2015] [Revised: 10/12/2015] [Accepted: 01/07/2016] [Indexed: 02/06/2023] Open
Abstract
The loss of cardiomyocytes during injury and disease can result in heart failure and sudden death, while the adult heart has a limited capacity for endogenous regeneration and repair. Current stem cell-based regenerative medicine approaches modestly improve cardiomyocyte survival, but offer neglectable cardiomyogenesis. This has prompted the need for methodological developments that crease de novo cardiomyocytes. Current insights in cardiac development on the processes and regulatory mechanisms in embryonic cardiomyocyte differentiation provide a basis to therapeutically induce these pathways to generate new cardiomyocytes. Here, we discuss the current knowledge on embryonic cardiomyocyte differentiation and the implementation of this knowledge in state-of-the-art protocols to the direct reprogramming of cardiac fibroblasts into de novo cardiomyocytes in vitro and in vivo with an emphasis on microRNA-mediated reprogramming. Additionally, we discuss current advances on state-of-the-art targeted drug delivery systems that can be employed to deliver these microRNAs to the damaged cardiac tissue. Together, the advances in our understanding of cardiac development, recent advances in microRNA-based therapeutics, and innovative drug delivery systems, highlight exciting opportunities for effective therapies for myocardial infarction and heart failure.
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33
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Hu LL, Zhang DD, Zhang Y, Shu Y, Chen XW, Wang JH. Glutathione functionalized mesoporous organosilica conjugate for drug delivery. RSC Adv 2016. [DOI: 10.1039/c6ra10841e] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
We developed a novel pH-responsive drug delivery system based on permeation-enhancing glutathione (GSH) and pH sensitive polyacrylic acid (PAA) grafted mesoporous organosilica nanocarriers (MONs).
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Affiliation(s)
- Lin-Lin Hu
- Research Center for Analytical Sciences
- College of Sciences
- Northeastern University
- Shenyang 110819
- China
| | - Dan-Dan Zhang
- Research Center for Analytical Sciences
- College of Sciences
- Northeastern University
- Shenyang 110819
- China
| | - Yang Zhang
- Research Center for Analytical Sciences
- College of Sciences
- Northeastern University
- Shenyang 110819
- China
| | - Yang Shu
- Institute of Biotechnology
- College of Life and Health Sciences
- Northeastern University
- Shenyang 110169
- China
| | - Xu-Wei Chen
- Research Center for Analytical Sciences
- College of Sciences
- Northeastern University
- Shenyang 110819
- China
| | - Jian-Hua Wang
- Research Center for Analytical Sciences
- College of Sciences
- Northeastern University
- Shenyang 110819
- China
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Budkov YA, Kolesnikov AL, Kiselev MG. Communication: Polarizable polymer chain under external electric field in a dilute polymer solution. J Chem Phys 2015; 143:201102. [DOI: 10.1063/1.4936661] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Affiliation(s)
- Yu. A. Budkov
- G. A. Krestov Institute of Solution Chemistry of the Russian Academy of Sciences, Laboratory of NMR Spectroscopy and Numerical Investigations of Liquids, Ivanovo, Russia
- Department of Applied Mathematics, National Research University Higher School of Economics, Moscow, Russia
| | - A. L. Kolesnikov
- Institut für Nichtklassische Chemie e.V., Universitat Leipzig, Leipzig, Germany
| | - M. G. Kiselev
- G. A. Krestov Institute of Solution Chemistry of the Russian Academy of Sciences, Laboratory of NMR Spectroscopy and Numerical Investigations of Liquids, Ivanovo, Russia
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35
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Pereira MC, Arachchige MCM, Reshetnyak YK, Andreev OA. Advanced targeted nanomedicine. J Biotechnol 2015; 202:88-97. [PMID: 25615945 PMCID: PMC4685670 DOI: 10.1016/j.jbiotec.2015.01.009] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2014] [Revised: 01/05/2015] [Accepted: 01/12/2015] [Indexed: 12/27/2022]
Abstract
Targeted drug delivery has been the major topic in drug formulation and delivery. As nanomedicine emerges to create nano scale therapeutics and diagnostics, it is still essential to embed targeting capability to these novel systems to make them useful. Here we discuss various targeting approaches for delivery of therapeutic and diagnostic nano materials in view of search for more universal methods to target diseased tissues. Many diseases are accompanied with hypoxia and acidosis. Coating nanoparticles with pH Low Insertion Peptides (pHLIPs) increases efficiency of targeting acidic diseased tissues. It has been showing promising results to create future nanotheranostics for cancer and other diseases which are dominating in the present world.
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Affiliation(s)
| | - Mohan C M Arachchige
- Department of Physics, University of Rhode Island, 2 Lippit Rd., Kingston, RI 028881, USA
| | - Yana K Reshetnyak
- Department of Physics, University of Rhode Island, 2 Lippit Rd., Kingston, RI 028881, USA
| | - Oleg A Andreev
- Department of Physics, University of Rhode Island, 2 Lippit Rd., Kingston, RI 028881, USA.
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36
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Takemura K, Ajiro H, Fujiwara T, Akashi M. A novel substrate for testosterone: biodegradable and biocompatible oil gel. Polym J 2015. [DOI: 10.1038/pj.2015.17] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
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37
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Zhang Y, Ding J, Sun D, Sun H, Zhuang X, Chang F, Wang J, Chen X. Thermogel-mediated sustained drug delivery for in situ malignancy chemotherapy. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2015; 49:262-268. [PMID: 25686948 DOI: 10.1016/j.msec.2015.01.026] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/06/2014] [Revised: 11/12/2014] [Accepted: 01/06/2015] [Indexed: 12/17/2022]
Abstract
In the past few decades, the in situ sustained drug delivery platforms present fascinating potential in sentinel chemotherapy of various solid tumors. In this work, doxorubicin (DOX), a model antitumor drug, was loaded into the thermogel of poly(lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(lactide-co-glycolide). The moderate mechanical property of DOX-loaded hydrogel was confirmed by rheological test. In vitro degradation revealed the good biodegradability of thermogel. The DOX-loaded hydrogel exhibited the sustained release profiles up to 30days without and even with elastase. The improved in vivo tumor inhibition and reduced side-effects were observed in the DOX-incorporated hydrogel group compared with those in free DOX group. The excellent in vivo results were further confirmed by the histopathological evaluation or terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. The thermogel with great prospect may be used as an ideal controlled drug delivery platform for the designated and long-term antitumor chemotherapy.
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Affiliation(s)
- Yanbo Zhang
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China; Department of Orthopedics, The Second Hospital of Jilin University, Changchun 130041, PR China
| | - Jianxun Ding
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.
| | - Diankui Sun
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China
| | - Hai Sun
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China
| | - Xiuli Zhuang
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China
| | - Fei Chang
- Department of Orthopedics, The Second Hospital of Jilin University, Changchun 130041, PR China.
| | - Jincheng Wang
- Department of Orthopedics, The Second Hospital of Jilin University, Changchun 130041, PR China.
| | - Xuesi Chen
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China
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38
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Li B, Lu X, Ma Y, Chen Z. Thermo- and pH-responsive behaviors of aqueous poly(acrylic acid)/poly(4-vinylpyridine) complex material characterized by ATR-FTIR and UV–Vis Spectroscopy. Eur Polym J 2014. [DOI: 10.1016/j.eurpolymj.2014.09.017] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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39
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Budkov YA, Kolesnikov AL, Georgi N, Kiselev MG. A statistical theory of cosolvent-induced coil-globule transitions in dilute polymer solution. J Chem Phys 2014; 141:014902. [DOI: 10.1063/1.4884958] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Affiliation(s)
- Yu. A. Budkov
- Institute of Solution Chemistry of the Russian Academy of Sciences, Ivanovo, Russia
| | - A. L. Kolesnikov
- Ivanovo State University, Ivanovo, Russia
- Institut für Nichtklassische Chemie e.V., Universitat Leipzig, Leipzig, Germany
| | - N. Georgi
- Max Planck Institute for Mathematics in the Sciences, Leipzig, Germany
| | - M. G. Kiselev
- Institute of Solution Chemistry of the Russian Academy of Sciences, Ivanovo, Russia
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40
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Takemura K, Ajiro H, Fujiwara T, Akashi M. Oil gels with a chemically cross-linked copolymer of a trimethylene carbonate derivative and l-lactide: preparation and stereocomplex formation within gels. RSC Adv 2014. [DOI: 10.1039/c4ra05341a] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Oil gels were prepared using chemically cross-linked copolymer, composed of poly(trimethylene carbonate) derivative and poly(l-lactide), possibly forming stereocomplex with poly(d-lactide).
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Affiliation(s)
- Kazuya Takemura
- Department of Applied Chemistry
- Graduate School of Engineering
- Osaka University
- Suita 565-0871, Japan
| | - Hiroharu Ajiro
- Department of Applied Chemistry
- Graduate School of Engineering
- Osaka University
- Suita 565-0871, Japan
- The Center for Advanced Medical Engineering and Informatics
| | - Tomoko Fujiwara
- Department of Chemistry
- The University of Memphis
- Memphis, USA
| | - Mitsuru Akashi
- Department of Applied Chemistry
- Graduate School of Engineering
- Osaka University
- Suita 565-0871, Japan
- The Center for Advanced Medical Engineering and Informatics
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